Association between preoperative hemoglobin with length of hospital stay among non-cardiac and non-obstetric surgery patients: a secondary analysis of a retrospective cohort study

Background Previous studies concerning the association between preoperative Hemoglobin (HB) level and the Length Of hospital Stay (LOS) in patients with non-cardiac surgery and non-obstetric surgery remain inconclusive. Herein, the objective of this study was to analyze whether and to what extent the preoperative HB level was connected with the LOS in non-cardiac and non-obstetric surgery patients. Methods This retrospective cohort study was performed at a single institution, involving patients who underwent elective non-cardiac, non-obstetric surgery from April 2007 to September 2013. Clinical characteristics of patients such as demographics, comorbidities, preoperative HB level, LOS, mortality, procedure length, and pulmonary hypertension (PHTN) Severity Class data were collected. A univariate analysis was used to determine the association between clinical characteristics and LOS. Multivariate regression analysis was conducted to investigate the relationship between preoperative HB level and LOS. Results and discussion In this study, 311 patients were included. We observed that compared with the LOS > 7 days group, the average HB level of patients in the LOS ≤ 7 days group was higher (12.04 ± 2.20 g/dl vs. 10.92 ± 2.22 g/dl, p < 0.001). In addition, there were fewer patients with moderate-to-severe anemia in LOS ≤ 7 days group than the LOS > 7 days group (32.74% vs 58.82%, p < 0.001). In addition, we found that patients with LOS ≤ 7 days were accompanied with lower mortality (0.44% vs. 7.06%, p < 0.001) and lower mean combined pulmonary artery systolic pressure (PASP) and right ventricular systolic pressure (RVSP) than that in patients with LOS > 7 days (42.56 ± 11.97 vs. 46.00 ± 12.37, p < 0.05). After controlling for relevant confounders, we discovered a nonlinear association between preoperative HB level and LOS as well as a threshold effect based on LOS. Specifically, when preoperative HB level was less than 11.9 g/dL, LOS decreased by 2 days for each 1 g/dL increase in HB level. However, LOS did not alter substantially with the rise of preoperative HB level when it was higher than 11.9 g/dL. Conclusion Our study showed a close non-linear association between preoperative HB level and LOS in patients with non-cardiac surgery and non-obstetric surgery. In particular, for patients with preoperative HB less than 11.9 g/dL, increasing the preoperative HB level can help shorten the LOS after operation. Supplementary Information The online version contains supplementary material available at 10.1186/s13019-024-02566-5.


Introduction
Anemia is a clinical common phenomenon with different incidence rate owing to the different diseases and different definition standards.A systematic review of surgical anemia showed the incidence of preoperative anemia ranging from 5 to 76% [1].In addition, it was reported that the incidence of preoperative anemia was 24-28.1% in patients undergoing cardiac surgery [2,3], whereas 28.7-30.44% in non-cardiac surgery patients [4,5].
Previous studies have demonstrated the association between preoperative anemia and adverse clinical outcomes, including prolonged hospitalization [6][7][8], increased mortality, and more serious complications [2,9].Among these, LOS has attracted a lot of attention in recent years as it is closely related to the patient's economic burden and quality of life.Indeed, numbers of studies have analyzed the effects of patient population data, comorbidities, preoperative laboratory indicators, and perioperative related factors, on LOS [10][11][12].However, few reports have addressed the effect of preoperative HB levels on LOS, especially in patients undergoing non-cardiac surgery and non-obstetric surgery.
Although some previous studies have analyzed the relation between preoperative HB and LOS in patients undergoing noncardiac surgery, most of them only analyzed the impact of patient population data, comorbidities, preoperative laboratory indicators, and perioperative related factors on LOS, but did not analyze the impact of PHTN on LOS.However, it should be pointed out that PHTN is common in surgical patients, and the perioperative surgical risk of such patients is higher than that of patients without PHTN, which may indicate that such patients will have a longer postoperative LOS.This study is based on a secondary analysis of previously published research data, and adds preoperative PHTN factors to previous studies to explore whether preoperative HB is still independently associated with LOS in patients with non-cardiac surgery and non-obstetric surgery.The threshold value of the impact of HB level on LOS can better illustrate the correlation between the two.
Taken these into consideration, this study conducted a secondary analysis based on previously published data, aimed to investigate whether and to what extent preoperative HB level was related to LOS in patients undergoing non-cardiac surgery and non-obstetric surgery.

Study population
Patients (age ≥ 18) who underwent elective non-cardiac, non-obstetric surgery under general anesthesia at a single institution (University of Washington Medical Center) from April 2007 to September 2013 were retrospectively investigated [13].In this study, we collected data from patient charts, including those admitted on the same day and those awaiting surgery.When patients had undergone multiple surgeries during a single hospital stay, we included only data from the initial surgery.Cases were excluded if: (1) data from two-dimensional echocardiography (ECHO) within 1 year prior to surgery were missing; (2) the patient was admitted to an inpatient ward or ICU bed > 24 h prior to the procedure; (3) there was absent or incomplete pre-procedure anesthesia clinic visit data; (4) the procedure or surgery was cancelled before or after administration of anesthesia.After excluding 238 patients with preoperative HB levels and loss of LOS and 2 patients with HB data outliers, 311 patients were finally enrolled for date analysis (Fig. 1).The clinicpathological features of the patients, such as age, gender, pre-procedure BMI, resting heart rate (HR), preoperative systolic (SBP) and diastolic blood pressure (DBP), tobacco use, preoperative comorbidities such as systemic Fig. 1 Flowchart of recruitment and research.Flowchart of the patient enrollment process in this study.A total of 311 patients were included in this study.In total, 226 patients were subgrouped into the LOS ≤ 7 days group and 85 patients were subgrouped into the LOS > 7 days group hypertension, coronary artery disease (CAD), congestive heart failure (CHF), arrhythmia, diabetes mellitus (DM), venous thromboembolism (VTE), asthma, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), and renal failure, preoperative laboratory indicators, such as creatinine level, and room air arterial oxygen saturation (SaO 2 ), were collected.The other data obtained by ECHO including left ventricular ejection fraction (EF), PASP, and RVSP, were also collected and analyzed.This project was approved by the University of Washington Institutional Review Board.
In this study, we first conducted a single-factor logistic regression analysis between each covariate and LOS to clarify the impact of each covariate on LOS, as shown in Table 2. Then we further screen for confounding factors that affect the relationship between HB and LOS (Additional file 1: Table S1-S4).The criteria for screening confounding factors are as follows: (1) The impact of introducing covariates in the basic model or removing covariates from the complete model on the regression coefficient of HB is > 10%; (2) The p value of the regression coefficient of the covariate on LOS is < 0.1; (3) variables meeting criteria 1 or 2 were used as confounders.Screened confounding factors include gender, American Society of Anesthesiologists (ASA) classification, procedure length, combined PASP and RVSP, mortality, intrathoracic, systemic hypertension, venous thromboembolism, asthma, renal failure (serum creatinine > 1.5 mg/dl), and heart rate.Multiple logistic regression analysis was used to further analyze the true relationship between HB and LOS without adjusting confounding variables and confounding factors.Different models in the data were adjusted based on the screenedout covariates.They are models that do not adjust any variables, Model I (only adjust the mortality variable), and Model II (only adjust all variables filtered out by criterion 1 or criterion 2).Additional file 1: Tables S1-S4 show the specific screening process.Smooth curve fitting was used to observe whether there was a nonlinear relationship between preoperative HB levels and LOS.When nonlinear associations were found, a two-piece linear regression model was applied to test for threshold effects.

Study parameters
Based on the World Health Organization (WHO) anemia standard [14], the preoperative HB level was divided into non-anemia group (male HB > 13 g/dL, female HB > 12 g/dL), mild anemia group (female HB 11-12 g/ dL, male HB 11-13 g/dL) and moderate-to-severe anemia group (HB < 11 g/dL).In addition, variables related to anesthesia and surgery were included, such as ASA class, procedure length, and mortality.Data from ECHO performed within a year of the index surgical date were collected.As for the severity of PHTN, it was divided into none PHTN (PASP or RVSP < 36 mmHg), mild PHTN (36 mmHg ≤ PASP or RVSP ≤ 50 mmHg), and moderateto-severe PHTN (PASP or RVSP > 50 mmHg) [15,16].Besides, LOS was defined as the interval from the date of surgery until the date of hospital discharge or in-hospital death.Prolonged LOS was defined as more than 7 days, which corresponds to the > 75th centile LOS of the data.

Statistical methods
Anonymized raw data were uploaded by Shah, Aalap C. et al. at the Datadryad Web site (www.datad ryad.org) with ownership authorized [13].Therefore, we further analyzed such data on a different hypothesis without violating the authors' rights.
All statistical analyses were conducted using the statistical software package R (http:// www.R-proje ct.org, The R Foundation) and Empower-Stats (http:// www.empow ersta ts.com, X&Y Solutions, Inc., Boston, MA).Normally distributed continuous variables are expressed as mean ± standard deviation (SD), and non-normally distributed continuous variables are replaced by median and interquartile range (IQR).Categorical variables are presented as totals and percentages.Multivariate multiple imputation with chained equations was used to impute missing data.Univariate analysis was used to determine the relation between clinical characteristics and LOS.Multivariate regression analysis was conducted to investigate the relation between preoperative HB level and LOS.A threshold, nonlinear association between HB and LOS was found in a generalized additive model (GAM).A p value < 0.05 was considered statistically significant.

Clinical characteristics of included patients
A total of 311 participants (151 males and 160 females) were selected for the final data analysis.Table 1 listed the baseline characteristics, operation-related and prognostic data of the selected participants according to LOS status.There were 226 (72.67%) patients in LOS ≤ 7 days group and 85 patients in LOS > 7 days group.No statistically differences were detected in age, gender, BMI, SBP, DBP, tobacco, white blood cell count, room air SaO 2 , serum creatinine, EF value between the two groups, respectively.In addition, preoperative comorbidities such as angina, coronary artery disease, arrhythmia, asthma, obstructive sleep apnea, renal failure (serum creatinine > 1.5 mg/dL), COPD and diabetes also showed no statistical difference between the two group.However, the mean preoperative HB level and systemic hypertension in LOS ≤ 7 days group showed significant differences compared to LOS > 7 days group, respectively.

Analysis of the associations between LOS and the clinical-pathological features of non-cardiac and non-obstetric patients
Preoperative anemia was present in 192 (61.74%) of 311 patients based on the WHO's gender-based criteria for anemia severity [14].We observed that the ratio of moderate-to-severe anemia in LOS > 7 days group was higher compared to LOS ≤ 7 days group (58.82% vs. 32.74%,p < 0.05).The proportion of mortality patients was 0.44% in LOS ≤ 7 days group and 7.06% in LOS > 7 days group (p < 0.001).Whereas procedure length, heart rate, combined PASP and RVSP were lower in LOS ≤ 7 days group than that in LOS > 7 days group, respectively (p < 0.05).Moreover, characteristics including intra-abdominal, intrathoracic, and PHTN severity class exhibited statistical difference between the two groups.
Due to a lack of data in few covariates such as blood pressure and heart rate, we then used multiple interpolation technology to supplement it (as detailed in Additional file 2: Table S5 and Additional file 3: Table S6).Based on this, we performed a univariate analysis to determine the association between clinical characteristics and LOS.Results in Table 2 showed that age, gender, BMI, SBP, DBP, heart rate, white blood cell count, room air SaO 2 , combined PASP and RVSP, PHTN severity class, angina, coronary artery disease, congestive heart failure, arrhythmia, venous thromboembolism, asthma, COPD, obstructive sleep apnea, renal failure, diabetes, and serum creatinine were not associated with LOS.However, tobacco, systemic hypertension, gender, and HB were negatively associated with LOS.In contrast, heart rate, intraabdominal, intrathoracic, venous thromboembolism, ASA IV, combined PASP and RVSP, PHTN severity class, procedure length, and mortality were positively associated with LOS.In addition, univariate analysis showed that the procedure length was closely associated with LOS.

Association between preoperative HB level and LOS in non-cardiac and non-obstetric patients
To better clarify the association between preoperative HB level and LOS in non-cardiac, non-obstetric surgery patients, we further conducted multiple regression analysis.Results of three models (non-adjusted model, Model I, and Model II) in Table 3 and 4 indicated that there was a negative association between preoperative HB level and LOS in non-cardiac, non-obstetric surgery patients, respectively (p < 0.0001).
For missing data on some covariates, we used multiple interpolation techniques to supplement and maximize statistical effects, and conducted a sensitivity analysis on the data.The results showed that the complete data analysis results after imputation were consistent with the multiple regression results excluding missing data (Additional file 2: Tables S5 and Additional file 3: Table S6).
Additionally, we found a nonlinear relation between preoperative HB level and LOS by cubic spline smoothing technique, and such a relationship still existed after adjusting for the confounding factors (Fig. 2).The inflection point of HB level was calculated to be 11.9 g/ dL (Table 5).When preoperative HB level < 11.9 g/dL, LOS decreased by 2 days for per 1 g/dL increase in HB level.However, when preoperative HB level > 11.9 g/dL, the estimated dose-response curve was consistent with

Discussion
This retrospective cohort study investigated the effect of preoperative HB level on LOS in non-cardiac and nonobstetric patients.By adjusting for the potential risk factors related to LOS, we showed that patients with prolonged hospitalization had a low preoperative HB level and a high prevalence of moderate-to-severe anemia, which were consistent with previous results [7,8,17].
These results indicate that more attention should be paid to this group of patients, so as to detect anemia-related symptoms in time and provide iron supplements, vitamin B12, and blood transfusion treatment when necessary.
In addition, we found that the incidence of preoperative anemia was 61.7% in non-cardiac and non-obstetric patients, and the incidence of mild and moderate-tosevere anemia was 21.9% and 39.9%, respectively.These results were in conflict with previous studies which indicated that the incidence of anemia in patients without cardiac surgery was 28.7-30.44%[4,5].Such a discrepancy could be explained by different patient characteristics and the definition criteria for anemia in different studies.Indeed, some researchers employed hemoglobin levels to define anemia, while others used hematocrit values.
Clinically, a lack of hematopoietic raw materials, including iron or folic acid, vitamin B12, and chronic diseases such as chronic infection, tumors, chronic renal insufficiency, etc., may lead to preoperative anemia [18].In addition, some patients may experience unexplained   [19].Moreover, preoperative anemia might increase postoperative mortality, the occurrence of complications, and negatively impact patients' postoperative activities and functional recovery [9,20].All of the above factors will lead to prolonged hospital stays and increased costs, which in turn highlights the importance of shortening hospital stays, as it can not only reduce medical insurance costs and save medical and health resources, but also increase bed turnover and reduce waiting times for elective surgeries.Previous research has shown a linear relationship between preoperative anemia and LOS, with one study suggesting that LOS would decrease by 0.2 days for every     1 g/dL increase in preoperative HB [17].In this study, we discovered a nonlinear association between preoperative HB level and LOS as well as a threshold effect based on LOS after controlling for relevant confounders.Specifically, when preoperative HB level was less than 11.9 g/dL, LOS decreased by 2 days for each 1 g/dL increase in HB.However, LOS did not alter substantially with the rise of preoperative HB level when it was larger than 11.9 g/ dL.Even though the results of this study on the relation between preoperative HB levels and LOS are inconsistent with previous studies.However, paying attention to the patient's anemia symptoms before and after surgery and providing timely treatment will be useful to reduce the patient's hospitalization time to a certain extent.At the same time, for patients undergoing non-cardiac and non-obstetric surgery, when the preoperative HB level is greater than 11.9 g/dL, adjusting the lipid level or blood glucose level may be also good for reducing the length of hospital stay, which requires further in-depth research.
It is necessary to point out the limitations of this retrospective study.First, some data were excluded due to the absence of certain preoperative HB level, resulting in a reduction in sample size and selection bias.Second, the clinical data came from a single center, leading to a lack of data on some covariates, such as treatment technology and ethnic differences.Consequently, a larger, multicenter investigation of individuals undergoing non-cardiac surgery and non-obstetric surgery may be necessary.

Conclusion
This study showed that preoperative anemia is prevalent among patients undergoing non-cardiac and nonobstetric surgery.The LOS was closely connected with the preoperative HB level, with a threshold and saturation effect.Therefore, careful monitoring and treatment of patients with preoperative anemia and adjustment of preoperative HB level to 11.9 g/dL or higher are important, which may help to shorten the LOS and reduce medical costs.

Fig. 2
Fig. 2 Association between HB and LOS.A threshold, nonlinear association between HB and LOS was found in a generalized additive model (GAM).Solid red line represents the smooth curve fit between variables.Blue bands represent the 95% of confidence interval from the fit.All adjusted for Heart Rate, tobacco, Renal failure (serum creatinine > 1.5 mg/dl), ASA classification, procedure length, mortality, Intrathoracic, systemic hypertension, and DBP Effect: LOS, Cause: HB Adjusted: Gender, ASA classification, procedure length, Combined PASP and RVSP, mortality, intrathoracic, systemic hypertension, Venous thromboembolism, Asthma, Renal failure (serum creatinine > 1.5 mg/dl), and Heart Rate CI Confidence Interval, LOS Length of Stay, HB hemoglobin, ASA American Society of Anesthesiologists, PASP pulmonary artery systolic pressure, RVSP right ventricular systolic pressure

Table 1
Baseline characteristics, operation-related and prognostic data of patients by LOS status (N = 311)

Table 1 (
LOS Length of Stay, ASA American Society of Anesthesiologists, BMI body mass index, SBP systolic blood pressure, DBP Diastolic Blood Pressure, COPD chronic obstructive pulmonary disease, ECHO echocardiography, SD Standard Deviation, IQR interquartile range, PASP pulmonary artery systolic pressure, PHTN pulmonary hypertension, RAP right atrial pressure, RVSP right ventricular systolic pressure, EF LeftVentricular Ejection Fraction continued) a horizontal line, suggesting a non-significant relation between HB level and LOS.

Table 2
Univariate analysis for LOS CI Confidence Interval, LOS Length Of Stay, ASA American Society of Anesthesiologists, BMI body mass index, SBP systolic blood pressure, DBP Diastolic Blood Pressure, COPD chronic obstructive pulmonary disease, ECHO echocardiography, IQR interquartile range, PASP pulmonary artery systolic pressure, PHTN pulmonary hypertension, RAP right atrial pressure, RVSP right ventricular systolic pressure, EF Left Ventricular Ejection Fraction

Table 3
Non-adjusted and adjusted linear regression models Gender, ASA classification, procedure length, Combined PASP and RVSP, mortality, Intrathoracic, systemic hypertension, Venous thromboembolism, Asthma, Renal failure (serum creatinine > 1.5 mg/dl), and Heart Rate CI Confidence Interval, LOS length of stay, HB hemoglobin, ASA American Society of Anesthesiologists, PASP pulmonary artery systolic pressure, RVSP right ventricular systolic pressure

Table 4
Non-adjusted and adjusted logistic regression models Non-adjusted model adjust for: None Model I adjust for: mortality Model II adjust for: Gender, ASA classification, procedure length, Combined PASP and RVSP, mortality, Intrathoracic, systemic hypertension, Venous thromboembolism, Asthma, Renal failure (serum creatinine > 1.5 mg/dl), and Heart Rate CI Confidence Interval, OR Odds Ratio, LOS Length of Stay, HB hemoglobin, ASA American Society of Anesthesiologists, PASP pulmonary artery systolic pressure, RVSP right ventricular systolic pressure

Table 5
Threshold Effect Analysis of HB and LOS using Piecewise Linear Regression